Treatment of cancer typically involves surgical resection, standard chemotherapy and/or radiation therapy to remove or kill tumor cells. However, the effectiveness of these treatments are often limited because of the invasiveness of the tumor and/or collateral damage to healthy tissues. Brain cancer is one of many types of cancer that can exhibit a limited response to traditional cancer treatment.
Glioblastoma (GBM) is the most common primary brain tumor and portends the worst prognosis among all central nervous system (CNS) malignancies (Deorah et al. 2006). Unlike other solid organ malignancies, GBMs are generally confined to the CNS and rare case reports of metastatic disease is rare (Ogungbo et al. 2005; Tuominene et al. 2005; Chivukula et al. 2005; Mourad et al. 2005; Rajagopalan et al. 2005; Utsuki et al. 2005).
The mean overall survival (OS) has only slightly improved over the last 30 years (Stupp et al. 2009). The current standard of care relies on surgical resection, fractioned radiotherapy and chemotherapy (Wen & Kesari 2008). The therapeutic efficacy of most of these treatment modalities is limited due to the invasive nature of the tumors. By the time gliomas are diagnosed they have often already infiltrated diffusely and are therefore extremely difficult to remove by complete surgical resection. The low oxygen level in the glioma environment negatively affects radiotherapy (Sheehan et al. 2010); while cellular heterogeneity and glioma stem cells account for the emergence of resistance to therapeutic regimens (Sampson et al. 2010; Bao et al. 2006). Therefore, there is an urgency to develop novel therapies capable of overcoming the common resistance mechanisms of gliomas (Dey et al. 2011).
The median survival after surgical intervention alone is approximately six months and the addition of radio-/chemotherapy can extend this time up to twelve months (Stupp et al. 2005a; Lesniak et al. 2004). Failed therapy is most often associated with local recurrence in the proximity of the original tumor (Gaspar et al. 1992). Consequently, efforts aimed at developing new therapies have focused on treatment strategies that target the tumor environment but spare normal and healthy surrounding brain cells. It would be desirable to generate new methods of treating GBM and other forms of cancer using such a strategy.